期刊
ONCOGENE
卷 31, 期 3, 页码 306-321出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/onc.2011.244
关键词
cell migration; CD146; ERM proteins; RhoA; RhoGDI1
资金
- National 863 Grant [2006AA02A245]
- National Basic Research Program of China (973 Program) [2009CB521704, 2011CB933503]
- National Important Science and Technology Specific Projects [2008ZX10004-005, 2008ZX10002-017, 2009ZX09102-247]
- National Natural Science Foundation of China [91029732]
- Chinese Academy of Sciences [KSCX2-YW-R-121, KSCX2-YW-R-173, KSCX2-YW-M15]
Tumor cell migration is a well-orchestrated multistep process that drives cancer development and metastasis. Previous data indicated that CD146 expression correlates with malignant progression and metastatic potential of human melanoma cells. However, the exact molecular mechanism of how CD146 promotes melanoma cell migration still remains poorly understood. Here, we report that CD146 physically interacts with actin-linking ezrin-radixin-moesin (ERM) proteins and recruits ERM proteins to cell protrusions, promoting the formation and elongation of microvilli. Moreover, CD146-promoted melanoma cell migration is linked to RhoA activation and ERM phosphorylation. CD146 recruits Rho guanine nucleotide dissociation inhibitory factors 1 (RhoGDI1) through ERM proteins and thus sequesters RhoGDI1 from RhoA, which leads to upregulated RhoA activity and increased melanoma cell motility. CD146-activated RhoA also promotes further ERM phosphorylation and activation through Rho-phosphatidylinositol-4-phosphate-5-kinase-phosphatidylinositol 4,5-biphosphate pathway, which reinforces CD146/ERM association. Thus, our results provide a mechanistic basis to understand the role of CD146 in regulating human melanoma cell motility. Oncogene (2012) 31, 306-321; doi:10.1038/onc.2011.244; published online 4 July 2011
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